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Chronic cough may be a result of neural hypersensitivity due to changes in both the peripheral and the central nervous systems, although the exact mechanisms underlying its pathogenesis are not completely understood. Opioid receptors, specifically kappa and mu, are potential therapeutic targets in the management of chronic cough because they play a pivotal role in both the peripheral and the central neural pathways implicated in the act of coughing. Morphine, a mu opioid receptor agonist, is an effective cough modulator; however, mu receptor agonists are part of a drug class that can induce respiratory depression and euphoria, with strong reinforcing properties that may lead to excessive use and abuse. Drugs with a dual-acting mechanism of kappa receptor agonism and mu receptor antagonism may be effective in the management of chronic cough without the potential for abuse. This review summarizes the current understanding of the mechanisms of cough hypersensitivity, the role of the kappa and mu receptors in the neurophysiology of cough, and the clinical potential of targeting these receptors as a novel way of managing chronic cough.<\/jats:p>","DOI":"10.1007\/s00408-025-00812-8","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T05:28:57Z","timestamp":1747114137000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Kappa and Mu Opioid Receptors in Chronic Cough: Current Evidence and Future Treatment"],"prefix":"10.1007","volume":"203","author":[{"given":"Surinder S.","family":"Birring","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter V.","family":"Dicpinigaitis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toby M.","family":"Maher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart B.","family":"Mazzone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive P.","family":"Page","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amale","family":"Hawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Sciascia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyn H.","family":"Morice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"issue":"1","key":"812_CR1","doi-asserted-by":"publisher","first-page":"1901136","DOI":"10.1183\/13993003.01136-2019","volume":"55","author":"AH Morice","year":"2020","unstructured":"Morice AH, Millqvist E, Bieksiene K, Birring SS, Dicpinigaitis P, Domingo Ribas C, Hilton Boon M, Kantar A, Lai K, McGarvey L et al (2020) ERS guidelines on the diagnosis and treatment of chronic cough in adults and children. 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AHM has received consulting fees from Bayer, Bellus Health Inc., Merck & Co, NeRRe Therapeutics, Shionogi Inc., and Trevi Therapeutics, Inc.; lecture fees from Boehringer Ingelheim, Merck & Co, and Chiesi Farmaceutici; and grant support from Bayer, Bellus Health Inc., Merck & Co, Nocion Therapeutics, Philips Pharma Group, NeRRe Therapeutics, Shionogi Inc., and Trevi Therapeutics, Inc. CPP has received consulting fees from Eurodrug Laboratories, Recipharm, Arcede Pharma, GlycoSynnovation, and Angelini Pharma not related to this review and is an NED for Ananda Developments Ltd. PVD has received consulting fees from Bayer, Bellus Health Inc., Chiesi Farmaceutici, Hyfe, Merck & Co, and Trevi Therapeutics, Inc. SBM has received consulting fees from Bellus Health Inc., Merck & Co, NeRRe Therapeutics, Reckitt Benckiser, Chiesi Farmaceutici, and Trevi Therapeutics, Inc.; and\u00a0grant support from Merck & Co and Reckitt Benckiser. SSB has received consulting fees from Bellus Health Inc., Merck & Co, Genentech, NeRRe Therapeutics, Nocion Therapeutics, and Trevi Therapeutics Inc.; lecture fees from AstraZeneca; and grant support from Merck & Co. TMM has received consultancy or advisory board fees from AbbVie Pharmaceuticals, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Endeavor BioMedicines, FibroGen, Inc., Galapagos, Galecto, Inc., GlaxoSmithKline, IQVIA, Merck & Co, Pliant Therapeutics, Pfizer, Qureight, Roche, Sanofi-Aventis, Structure Therapeutics, Trevi Therapeutics, Inc., and Vicore Pharma. TS is employed by Trevi Therapeutics, Inc., as Chief Scientific Officer and a Corporate Officer.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"62"}}